Abstract: Head and Neck Cancer Program (HNCP) The overarching mission of the Head and Neck Cancer Program (HNCP) is to translate basic discoveries from member laboratories into clinical trials for HNC patients and to take observations from the clinic back to the bench to elucidate mechanisms and advance the prevention, detection and treatment of this malignancy. To achieve this goal, HNCP promotes and facilitates collaborative interactions and innovative discoveries among investigators along the entire continuum of basic, translational, and clinical HNC research. To address the heterogeneity of HNC and the need for more effective treatment approaches, the HNCP is organized around three translational research themes, each represents interdisciplinary interactions between research laboratories and clinical investigators with the primary objective to develop investigator-initiated clinical trials to test discrete hypotheses: 1) window-of-opportunity platform trials; 2) targeting resistance mechanisms; and 3) precision genomic medicine. The specific aims of the HNCP are to: 1) determine the pharmacodynamic, immune and/or anti-viral effects of molecular targeting and immunotherapeutic agents with demonstrated preclinical activity in HNC using neoadjuvant or window-of-opportunity clinical trial platforms; 2) optimize clinical responses to standard therapeutics in HNC, including epidermal growth factor receptor (EGFR) inhibitors, cisplatin and radiation by targeting alternative molecular or immune resistance pathways; and 3) identify predictive biomarkers of treatment responses. The HNCP has 25 members representing 10 academic departments and 3 schools of the University of Pittsburgh. Members of the Program currently receive a total of $3.9 M in annual direct funding, including $2.3 M from the NCI and $1.1 M in other peer-reviewed grant support. The HNCP is home to an NCI Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer, which was renewed in 2010. Between January 2010 and April 2014, Program members published 299 papers, including high-impact publications in Science, PNAS, JCI, Cancer Discovery, and JCO, of which 49% resulted from intra-programmatic and 36% from inter-programmatic collaborations. Approximately 38% of the papers represent collaborations with external investigators. Nearly all of the members who joined the Program during this funding period were new recruits to UPCI, reflecting the critical importance of the HNCP to the translational research efforts of UPCI. UPCI support, including Clinical Protocol and Data Management and Shared Resources, specifically the Animal Facility, Biostatistics Facility, Cancer Bioinformatics Services, Cancer Genomics Facility, Cancer Pharmacokinetics and Pharmacodynamics Facility, Cancer Proteomics Facility, Cell and Tissue Imaging Facility, Chemical Biology Facility, Cytometry Facility, Immunological Monitoring and Cellular Products Laboratory, In Vivo Imaging Facility, Investigational Drug Services, and Tissue and Research Pathology Services facilitates and enhances HNCP research.